Disorders of bone marrow function and hemopoietic cell renewal constitute a major clinical problem and include such diverse diseases as the leukemias, polycythemia vera, aplastic anemia, myelofibrosis, etc. An understanding of the mechanisms by which hemopoiesis is controlled is clearly of importance in the eventual understanding and improved treatment of these clinical disorders. Our long-range objective is to gain insight into the mechanisms responsible for control or production of the pluripotent stem cell, its more committed progeny, and the differentiated elements of the bone marrow and the interrelationship of these formed elements with the microenvironment and bone marrow structure. Our immediate objective is to develop a technique for quantification of myelopoiesis in vivo, and to further define the physiologic role of the colony stimulating factor, (? granulopoietin) its mode of production and its relationship to endotoxemia using both in vitro and in vivo techniques. We would also propose to explore further the factors controlling migration of the pluripotent and committed stem cells, to examine the interrelationship of the immune system and more particularly the thymus with the regulation of the pluripotent stem cell, and to develop an experimental model for aplastic anemia.